1. Field of the Invention
This invention relates to topical application of a cream, gel, or other vehicle which contains substances such as L-arginine which delivers these substances into tissue for the purpose of producing beneficial effects such as warming of cold or cool tissues, growth of hair on the scalp, healing of leg ulcers secondary to diabetes or confinement to bed, as well as beneficial effects through restoration of natural mechanisms based on improvement of local blood supply.
2. Prior Art
Approaches to improving local blood flow have been many and consist of both systemic and topical approaches. Many beneficial effects could be obtained should improvement in local blood flow be achieved since impairment of local blood flow causes a variety of negative consequences. Among these are cold hands and feet, baldness, leg ulcers, certain forms of impotence, as well as a variety of other things. There have been several attempts to warm cold tissue including cold hands, fingers, feet and toes. Many persons suffer from cold hands, feet or other body parts. This is often caused by insufficient blood flow in the cold tissue. Previously cold hands or feet have been treated by wearing warm socks or gloves, sometimes even socks or gloves which are mechanically heated. The use of hot packs and glove or shoe inserts which generate heat through chemical reactions has also been a potential solution. These approaches have obvious disadvantages, for example, in maintaining finger dexterity. Certain liniments containing, such as capsicum have been suggested. More recently, topical creams containing nitroglycerine have been used. See H. Natsuda et al., Ryumachi 34, 849 (1994). While these medicaments have enjoyed some level of success, the effects are often extremely transient in nature. Nitroglycerine creams also have the significant disadvantage that nitroglycerine is a cardioactive drug, raising concerns of effects on the heart.
The fundamental basis for cold tissue of the hands, fingers, feet and toes as well as other cold tissue is insufficient blood flow to the. tissue. It has been suggested by some that the use of increased blood flow through relaxation of blood vessels, particularly small and very small vessels may be of use in warming cold tissue. However reasonable this suggestion, many attempts to demonstrate warming by use of agents which produce vasodilation and therefore increased blood flow have produced negative results. See N Dietz et al., J Appl Physiol 76, 2047 (1994); S Whitmore et al., J Rheumatol 22, 50 (1995); S Singh et al., Eur J Clin Invest 25, 182 (1995). The only report of modest temporary success involved the use of nitroglycerine. See H Natsuda et al., Ryumachi 34, 849 (1994). The oral administration of the nitric oxide precursors, such as L-arginine, to produce warming secondary to vasodilation has been suggested. And a variety of indirect and non-definitive experiments have been conducted. See M. Sonntag et al., Pflugers Arch 420, 194 (1992); A. Agostoi et al., Int J Clin Lab Res 21, 202 (1991). Thus, while the literature contains suggestions that vasodilation by administration of oral L-arginine, the precursor of nitric oxide (endothelium-dependent relaxing factor), no reports exist of success in producing an actual warming of tissue using this agent. In fact Dietz (see N Dietz et al., J Appl Physiol 76,2047 (1994)) concludes from his data that "These data suggest that NO (nitric oxide) does not play a major role in cutaneous vasodilation during body heating in humans." Further Singh (see S Singh et al., Eur J of Clin Invest 25, 182 (1995)) in a study of patients with Raynaud's phenomenon (severely cold hands and/or feet) concludes that L-arginine, administered orally, failed to cause vasodilation (and therefore warming) in patients with Raynaud's phenomenon.
Accordingly, several objects and advantages of the instant invention are to warm cold tissue in hands, feet or other tissue by increasing blood flow in the tissue means of enhancement of the body's natural mechanisms. It is further an object and advantage of the instant invention to prophylactically prevent tissue from becoming cold by use prior to entering into situations which induce cold hands and feet such as skiing or other winter outdoors activities.